A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Varegacestat in Participants With or Without Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- PK of varegacestat and metabolite from a single oral dose of varegacestat in hepatic impaired adult participants to matched healthy adult participants.
研究概览
简要总结
This clinical trial is designed to determine the pharmacokinetics, safety and tolerability of varegacestat in people with impaired liver function compared to people with normal liver function.
详细描述
This is an open-label, single-dose, parallel study to evaluate the effects of varying degrees of impaired hepatic function on the PK, safety, and tolerability of varegacestat in adult participants.
The study will be conducted sequentially. The study will enroll participants with mild (Group 2) and moderate (Group 3) hepatic impairment (HI) and healthy participants with normal hepatic function (Group 1) at a 1:1 ratio. Matched healthy participants may match to more than one participant in the HI groups. Subsequently, if appropriate, the study will enroll participants with severe (Group 4) HI and healthy participants with normal hepatic function (Group 1), as needed, to provide 1:1 matches for Group 4. The decision to conduct Group 4 enrollment will be contingent upon the assessment of the feasibility, PK, and safety data from Groups 1-3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(Healthy Participants):
- •Healthy, adult, male or female (of nonchildbearing potential only), 18 to 84 years of age, inclusive, at the screening visit. Participant will be matched by age (± 10 years) and sex to a participant with hepatic impairment (HI). Each healthy participant may be matched to more than 1 participant with HI, but cannot be matched to more than 1 participant within the same HI group.
- •Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee
- •Inclusion Criteria (Hepatic Impairment):
- •Healthy, apart from HI, adult male or female (of nonchildbearing potential only), 18 to 84 years of age, inclusive, at the screening visit.
- •Considered to have HI (of any etiology) that has been clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to dosing per the PI and Sponsor and is likely to remain stable throughout the study. To be classified as having hepatic impairment with known medical history of liver disease (with or without a known history of alcohol abuse).
- •Has a score on the Child-Pugh scale at screening visit and confirmed at check-in as follows:
- •Mild: ≥5 and ≤6 [Category A]; or
- •Moderate: ≥7 and ≤9 [Category B]; or
- •Severe: ≥10 and ≤15 [Category C].
- •- Medically healthy, apart from HI, with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee
排除标准
- •(Healthy Volunteers):
- •Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.
- •Exclusion Criteria (Hepatic Impairment):
- •Participants must not be enrolled in the study, if they meet any of the following criteria:
- •Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical (except for HI) or psychiatric condition or disease in the opinion of the PI or designee.
- •History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.
研究组 & 干预措施
Treatment Arm
Single oral dose of varegacestat administered on study day 1
干预措施: varegacestat (Drug)
结局指标
主要结局
PK of varegacestat and metabolite from a single oral dose of varegacestat in hepatic impaired adult participants to matched healthy adult participants.
时间窗: Up to 4 weeks
AUC0-t varegacestat and metabolite
次要结局
- Assess the safety and tolerability of a single oral dose of varegacestat in hepatic impaired adult participants and in matched healthy adult participants.(Up to 4 weeks)